Elsevier

Steroids

Volume 69, Issues 11–12, October–November 2004, Pages 763-766
Steroids

Licorice reduces serum testosterone in healthy women

https://doi.org/10.1016/j.steroids.2004.09.005Get rights and content

Abstract

Licorice has been considered a medicinal plant for thousands of years. The most common side effect is hypokalemic hypertension, which is secondary to a block of 11β-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid effect of cortisol. We have investigated the effect of licorice on androgen metabolism in nine healthy women 22–26 years old, in the luteal phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6% W.W. of glycyrrhizic acid) daily for two cycles. They were not on any other treatment. Plasma renin activity, serum adrenal and gonadal androgens, aldosterone, and cortisol were measured by radioimmunoassay. Total serum testosterone decreased from 27.8 ± 8.2 to 19.0 ± 9.4 in the first month and to 17.5 ± 6.4 ng/dL in the second month of therapy (p < 0.05). It returned to pre-treatment levels after discontinuation. Androstenedione, 17OH-progesterone, and LH levels did not change significantly during treatment. Plasma renin activity and aldosterone were depressed during therapy, while blood pressure and cortisol remained unchanged.

Conclusions:

licorice can reduce serum testosterone probably due to the block of 17-hydroxysteroid dehydrogenase and 17–20 lyase. Licorice could be considered an adjuvant therapy of hirsutism and polycystic ovary syndrome.

Introduction

Licorice has been used as a medicinal plant for thousands of years. The active component of licorice, glycyrrhizic acid, is hydrolyzed in vivo to glycyrrhetinic acid, which is responsible for most of its pharmacological properties. In ancient Chinese medicine and during Roman times, licorice was also recommended to cure sterility of women [1], [2]. Theophrastus and Pliny also reported an efficacy of licorice in reducing hunger and thirst [1], [3]. In addition licorice extract has some estrogen-like, anti-viral, and antioxidant properties [1].

The most common side effect of chronic consumption of high amounts of licorice is hypokalemic hypertension, which is due to the block of the activity of 11β-hydroxysteroid dehydrogenase type 2 (11HSD2) at the level of the kidney and of other classical targets for aldosterone [4], [5], [6]. In these tissues, this enzyme plays a key role in modulating mineralocorticoid effects by inactivating cortisol to cortisone [4], [5], [6]. In addition, glycyrrhetinic acid can bind directly to mineralocorticoid receptors as an agonist when its plasma concentration is high enough to compete with aldosterone and cortisol for mineralocorticoid receptors [4], [7], [8].

Licorice is also able to affect androgen metabolism [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. Various studies have demonstrated that licorice blocks the activity of 3-β-hydroxysteroid dehydrogenase (3HSD), 17-hydroxysteroid dehydrogenase (17HSD) and 17–20 lyase [9], [10], [11], [12], [13], [14], [15], [16] and stimulates the activity of aromatase [14]. All these enzymes are involved in the synthesis and/or metabolism of androgens and estrogens. A possible compensatory mechanism is the binding of glycyrrhetinic acid to sex binding globulin, thus increasing free testosterone and estradiol values [17].

Licorice can also affect the ratio 5α-/5β ring A reduced steroids, particularly of glucocorticoids and their metabolites, as demonstrated by the increase of the 5α-/in relation to 5β-reductase activity [13], [18]. It is known that 5α-reductase also affects the conversion of testosterone into dihydrotestosterone, and therefore this mechanism can affect the metabolism of androgens particularly in man.

Yaginuma et al. showed an effect of an herbal product containing glycyrrhizic acid in the reduction of serum testosterone and induction of regular ovulation [20]. Takeuchi et al. reported that glycyrrhizic acid affects the in vitro conversion of androstenedione to testosterone and stimulates aromatase activity, promoting the production of estrone and estradiol [16]. In males, we demonstrated a reduction of total serum testosterone after 1 week of therapy with high amounts of licorice [9], [10].

Now, we have studied the effect of prolonged consumption of licorice on serum androgens in healthy women.

Section snippets

Experimental

Nine healthy women aged 22–26 years from the staff of the Department of Medical and Surgical Science of the University of Padua were enrolled for this study. The study was approved by the local ethics committee and all the volunteers gave their informed consent. The subjects had normal BMI (23.4 ± 2.1), were regularly menstruating, and did not take contraceptives or other substances that could interfere with the hormonal measurements. None of the subjects showed clinical, ultrasonographic, or

Results

Results are reported in Table 1 and Fig. 1. We did not find any significant change in the mean diastolic and systolic blood pressure either before treatment (110.5 ± 9.7/70.0 ± 8.8 mmHg), at the end of treatment (116.9 ± 9.2/73.1 ± 10.3 mmHg), or after discontinuation (112.7 ± 6.5/69.4 ± 7.3 mmHg).

Total serum testosterone decreased from a mean of 27.8 ± 8.2 ng/dL to 19.0 ± 9.4 ng/dL after one cycle (p < 0.05) and to 17.5 ± 6.4 ng/dL after two cycles (p < 0.05). After discontinuation, testosterone returned to pre-treatment

Discussion

In our subjects, licorice produced the known effects on the renin-angiotensin–aldosterone system and on cortisol metabolism [4], [5]. PRA remained suppressed after 1 month of licorice withdrawal, consistent with a more prolonged effect of volume expansion on the renin angiotensin system.

Serum cortisol was unchanged since the effect of licorice on 11HSD2 is mainly at the level of the kidney, and this effect is usually evident in urinary metabolites of cortisol. Aldosterone was thus reduced, due

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